Soft tissue volume augmentation has become one of the major challenges in dental and cranio-maxillofacial surgery. In order to improve both functional and esthetic outcomes by soft tissue volume augmentation, autogenous tissue grafts such as the free gingival graft (FGG) or the subepithelial connective tissue graft (SCTG), despite their drawbacks are still broadly used for various indications and considered to be the gold standard (F. Cairo et al., 2008, J. Clin. Periodontol. 35 (Suppl. 8), 314-319; R. Jung et al., 2004, Int. J. Periodontics Restorative Dent. 24(6), 545-553 and D. Thoma, 2009, Clin. Oral Implants Res. 20 (suppl. 4), 146-165). However, the harvesting procedure for autogenous tissue at a second surgical site usually in the palate has drawbacks for the patient and limitations as to the quality and quantity of tissue that can be retrieved.
A regenerative device for promoting soft tissue volume augmentation in the oral region is thus desirable.
Gingival cells of the oral connective tissue are exposed to complex mechanical forces during mastication, swallowing, tongue movement, speech, tooth movement and orthodontic treatment. Especially during wound healing following surgical procedures, internal and external forces may occur, creating pressure upon the regenerative device and newly formed tissue.
A regenerative device has to meet certain criteria before being used in the oral cavity for soft tissue volume augmentation: It must be biocompatible, resorbable in vivo, allow gingival ingrowth, show a good level of tissue integration such as to allow uneventful healing (without excessive inflammation or dehiscence) and be able to withstand mechanical forces by acting as a scaffold that maintains tissue volume during a sufficient time during the wound healing process after implantation, generally at least about 3 months.
No such regenerative device has so far been disclosed in the prior art.
H. Mathes et al. in “A Bioreactor Test System to mimic the Biological and Mechanical Environment of Oral Soft Tissues and to Evaluate Substitutes for Connective Tissue Gaffs”, 2010, Biotechnology and Bioengineering, Vol. 9999, No. 9999, disclose that such properties of a regenerative device consisting of a collagen sponge might be achieved by stiffening the matrix body by crosslinking of the collagen fibers to a degree allowing the right balance between mechanical stability (high degree of crosslinking) and uneventful soft tissue healing (low degree of crosslinking), but are totally silent on how to prepare such a collagen sponge. They disclose that three different collagen sponge prototypes consisting of porcine collagen type I and Ill with an average pore diameter of 92 μm and 93% porosity and differing in their degree of crosslinking (prototypes provided by Geistlich Pharma, Wolhusen, Switzerland) showed after culture under mechanical stimulation for 14 days a satisfying volume retention with a good fibroblast cell vitality.
DS Thoma et al. in “Soft tissue volume augmentation by the use of collagen-based matrixes: a volumetric analysis”, 2010, J. of Clin. Periodontology 37, 659-666, and “Soft tissue volume augmentation by the use of collagen-based matrixes in a dog mandible—a histological analysis”, 2011, J. Clin. Periodontol.: 38:1063-1070, disclose that one of the collagen sponge prototypes referred to in the above publication of H. Mathes et al. showed after a period of 28 or 84 days of implementation into a chronic ridge defect of a dog mandible the same volume retention as the gold standard, SCTG (subendopithelial connective tissue graft).
The prior art does not disclose or suggest what are the features of such a chemically crosslinked collagen sponge prototype, or of any other regenerative collagen device fulfilling the criteria set forth above for a use in the oral cavity for soft tissue volume augmentation, or how such a device can be prepared.
EP-1561480 discloses a resorbable collagen device for use as a dural substitute for growing meningeal tissue, comprising a chemically crosslinked collagen sheet which has a majority of pores below 10 μm and a method for preparing that collagen device comprising the steps of mixing collagen with water under such conditions that the mixture contains substantially solubilized collagen, lyophilizing the mixture into a collagen device and chemically crosslinking the collagen device, using as crosslinking agent formaldehyde or gluteraldehyde. A dural substitute is not, like a regenerative device for promoting soft tissue volume augmentation in the oral region, exposed during wound healing to pressure created by the above mentioned complex mechanical forces.
US-2004-0265785 describes a process for producing a collagen-elastin membrane containing at least 20% (w/w) elastin, comprising the steps of first chemically removing hydrophobic accompanying substances from an elastin containing collagen material of natural origin, then chemically removing non-hydrophobic substances. The collagen-elastin product is not chemically crosslinked.
Boekema B. K. L. H. et al., 2014, Journal of Material Sciences: Materials in Medicine, Feb. 2014 25: 423-433, describe the effect on wound healing of pore size and crosslinking on collagen-elastin scaffolds used as dermal substitutes. The disclosed EDC-NHS chemically crosslinked scaffolds contain 10-15% elastin, have a pore size of 80 to 120 μm and a denaturation temperature of 64 to 69° C. (see Table 1, page 425). They are sterilized by ethylene oxide gas treatment. The authors conclude that crosslinking negatively affects wound healing on several important parameters, notably by reducing the ability of fibroblasts to proliferate and replace the dermal substitute by new tissue. A dermal substitute is not, like a regenerative device for promoting soft tissue volume augmentation in the oral region, exposed during wound healing to pressure created by the above mentioned complex mechanical forces.
The problem or objective of the invention is to find a regenerative collagen device for promoting soft tissue volume augmentation in the oral region that is biocompatible, resorbable in vivo, allows gingival ingrowth, shows a good level of tissue integration such as to allow uneventful healing (without excessive inflammation or dehiscence) and be able to withstand mechanical forces by acting as a scaffold that maintains tissue volume during a sufficient time during the wound healing process after implantation, generally at least about 3 months.
The above problem is solved by the invention as defined in the appended claims.